Abstract
Interaction of apolipoprotein (apo) A-I with lipid membrane is involved in a large number of processes in lipoprotein metabolism and cholesterol homeostasis. This review discusses the molecular mechanisms of interaction of
apoA-I with lipid membrane in view of their structures. Lipid-free apoA-I is folded into two domains, comprising an Nterminal part forming a four-helix bundle and a discrete C-terminal part. It is well known that insertion of a proline
residue into a protein sequence disruptsα-helix structure. Perturbation of the helix bundle structure occurs by the
proline insertion into the putative helical region in the N-terminal domain, suggesting that the substituted residue is
part of the helix bundle.
In lipid-binding, apoA-I recognizes headgroup separation (hydrated space) between phospholipid molecules at the
lipid membrane. ApoA-I initially binds to lipid through the C-terminal domain, followed by a conformational opening
of the helix bundle with an accompanying increase inα-helical content. The transition from random coil toα-helix
has been shown to produce a large negative enthalpy (exothermic heat) that drives lipid binding. Despite a lack of
the C-terminal domain, which is critical for lipid-binding, perturbation of the helix bundle structure restored the lipidbinding ability by exposing a potential lipid-binding region in the N-terminal domain.
